Diabetic retinopathy (DR) is characterized by capillary nonperfusion, vascular hyperpermeability, and neovascularization, and is a leading cause of blindness. Capillary nonperfusion, in particular, is an early indicator of DR and increases with severity of DR. The Early Treatment of Diabetic Retinopathy Study (ETDRS) qualitatively evaluated macular ischemia using fluorescein angiography (FA) and found it to have predictive value for progression of disease. Such rigorous grading of FA as used in the ETDRS study, however, is impractical for clinical practice. FA also suffers from several additional shortcomings, including dependence on early transit for macular capillary details, dye leakage which obscures of details of vascular structure, and variability of contrast. These limitations have hampered the clinicians' ability to assess nonperfusion objectively using FA. Thus, there remains an unmet need for an accurate, objective, and automated method to evaluate macular ischemia. Such a method would provide a valuable biomarker for DR with in-clinic applicability.
Optical coherence tomography angiography (OCTA) is an extension of structural optical coherence tomography (OCT) that can provide high-contrast imaging of capillary details without the need for dye injection. As such, OCTA provides a method to objectively evaluate capillary structure and health in a clinical setting. OCTA data can be used to automatically quantify total avascular area (AA) in the inner retina, and can detect DR with high sensitivity and specificity for patients having proliferative DR, the more advanced stage of the disease. However, detection of less severe forms of DR nonproliferative diabetic retinopathy (NPDR) remains a challenge. Part of the challenge is due to retinal anatomy: the inner retina is composed of three distinct, but tightly stacked, plexuses that are difficult to resolve into individual layers via OCTA because of projection artifacts. However, a new technique called Projection-resolved (PR) OCTA can be used to reduce the problem of projection artifacts blurring the plexuses together (e.g., as described in Zhang M, Hwang T S, Campbell J P, et al. Projection-resolved optical coherence tomographic angiography. Biomedical Optics Express 2016; 7:816-828, hereby incorporated by reference herein). Using PR-OCTA, individual plexuses revealed more areas of capillary drop out than seen in inner retinal angiograms of the plexuses. However, this increased sensitivity to detect capillary nonperfusion within individual plexuses is still susceptible to substantial noise artifacts. These noise artifacts degrade the integrity of imaged capillary structures and introduce spurious signal noise in non-capillary space, making quantification of AA less reliable and less reproducible. Thus, there remains a need for improved image processing methods to calculate AA in a robust and reliable manner.